Congenital anomalies are the second leading cause of perinatal mortality in the United States after premature birth. Advances in imaging techniques have allowed the detection of many anatomical defects with ultrasound before birth. The goal of this project is to improve the diagnosis and treatment of fetal disease and congenital anomalies. The Perinatology Research Branch has initiated a series of projects to improve the detection of congenital anomalies and assess fetal growth and development with the use of three-dimensional ultrasound. The findings of this year include the following: 1. Three-dimensional (3D) color power imaging of fetal hepatic circulation: The anatomy and physiology of the fetal hepatic system are complex. Yet, their evaluation is of considerable importance in assessing the hemodynamic status of a critically ill fetus. Furthermore, congenital anomalies of this circulatory system are relatively common and difficult to identify with conventional two-dimensional (2D) imaging techniques. The purpose of this study was to determine how automated 3D power Doppler ultrasonography defines the normal anatomy of the fetal portosystemic and umbilical venous systems and identifies fetal hepatic vascular anomalies. In a prospective study, the hepatic and umbilical venous systems were imaged in 390 fetuses with 2D ultrasonography, color and spectral Doppler imaging. Vascular abnormalities were observed in 2.6% of fetuses (n=8). The anomalies were: absent ductus venosous, n=4; direct connection between the umbilical vein and the right atrium, n=2; and direct connection between the umbilical vein and the inferior vena cava, n=2. This study demonstrated that 3D color power Doppler ultrasonography can be used to image normal fetal hepatic and portal circulation and identify anomalies of the fetal portosystemic and umbilical venous sytems. 2. Four-dimensional ultrasonography of the fetal heart with spatio-temporal image correlation: Congenital heart disease is the leading cause of infant mortality related to birth defects with a prevalence ranging from 4-11/1,000 births. Prenatal diagnosis remains a major challenge. Four-dimensional (4D) ultrasonography is a technology that incorporates motion to 3D imaging. Spatio-temporal image correlation (STIC) is a recent advance that allows dynamic multiplanar slicing and surface rendering of heart anatomy. Fetal heart volumes are acquired with a single automated sweep of the transducer. Spatial and temporal information are combined to display dynamic images that can be extracted from volume datasets. Standardized viewing planes, such as the one recommended by the AIUM, can be analyzed. In addition, planes not routinely feasible with 2D ultrasonography can be generated. This year, the Branch reported the utilization of STIC for the examination of the fetal heart and the diagnosis of congenital anomalies. Volume datasets obtained were utilized to demonstrate the cardiac chambers, moderator band, interatrial and interventricular septae, atrioventricular valves, pulmonary veins and outflow tracts. With the use of a reference dot to navigate the four-chamber view, intracardiac structures could be simultaneously studied in three orthogonal planes. The same volume dataset was used for surface rendering of the atrioventricular valves. The aortic and ductal arches were best visualized when the original plane of acquisition was sagittal. Volumes could be interactively manipulated to simultaneously visualize both outflow tracts, in addition to the aortic and ductal arches. Novel views of specific structures were generated. Dynamic multiplanar slicing and surface rendering of the fetal heart are feasible with STIC technology. One good quality volume dataset, obtained from a transverse sweep, can be used to examine the four-chamber view and the outflow tracts. This novel method may assist in the evaluation of fetal cardiac anatomy. 3. Three-dimensional ultrasound fetal lung volume measurement: a systematic study comparing the multiplanar method with the rotational (VOCAL) technique: Prenatal diagnosis of pulmonary hypoplasia is a major clinical challenge. The diagnosis is made at autopsy by demonstrating low lung weight and a low lung:body ratio. Several fetal biometric parameters have been used to predict the likelihood of lethal pulmonary hypoplasia of the newborn, however, nearly all parameters developed thus far are less than optimal. 3D ultrasound may improve the estimation of fetal organ size. Additionally, rotational measurement of volume has now become possible through the recent introduction of a software tool named VOCAL (Virtual Organ Computer-aided AnaLysis, 3D View). The software allows volume calculation by rotation the organ of interest around a fixed axis through a number of sequential steps. Thirty-two fetuses with a variety of conditions at risk for pulmonary hypoplasia were studied. 3D volume data sets of the fetal lungs were acquired using a commercially available ultrasound system. The right and left lung volumes were calculated separately using VOCAL and the multiplanar technique. The level of agreement between two independent observers in categorizing the 3D volume data set as measurable or non-measurable was determined. The interobserver and intermethod variabilities were also evaluated for both methods. The intermethod variability was excellent (correlation r=0.93 and r=0.96 for the left and right lung, respectively), and there was substantial agreement between the results of both approaches (limits of agreement -4.4 to 8.9 and -3.4 to 4.8 mL for the right and left lung, respectively). Fetal lung estimation with VOCAL had a significantly higher interobserver variability than the multiplanar technique. Interobserver agreement in categorizing lung volume data sets as measurable or non-measurable was lower when VOCAL was used. Fetal lung volume measurements can be undertaken interchangeably using the multiplanar technique or the rotational method with VOCAL. However, the latter was less reproducible (lower degree of agreement and significantly higher interobserver variability) than the former. 4. Genetic Sonography: An option for women of advanced maternal age who are screen-negative following triple-marker maternal serum screening: The prenatal detection of trisomy 21 is a major goal in prenatal care for families who seek antenatal diagnosis. Several approaches are available including 1) routine offering of amniocentesis to women age 35 and over; 2) maternal serum screening and identification of patients at risk; and 3) a combination of the previous two with a sonographic examination of the fetus. Trisomy 21 is often associated with phenotypic abnormalities, which could be detected with ultrasound. The Branch conducted a study to determine whether offering genetic ultrasound to patients 35 years and older who are screen-negative following maternal serum triple-marker screening is cost-effective and will result in an increase in the detection rate of trisomy 21. The detection rate and cost of detecting trisomy 21 were determined in women 35 years and older managed according to the following three policies: (I) universal genetic amniocentesis; (II) maternal-serum triple marker screening followed by amniocentesis only in high-risk women (risk greater than 1:90); and (III) genetic ultrasound in women who were screen-negative (policy II). Policy III included offering genetic amniocentesis to patients with an abnormal genetic ultrasound. In conclusion, the Branch found that offering genetic ultrasound followed by amniocentesis to patients 35 years and older that were originally screen-negative following triple-marker maternal serum screening for the diagnosis of trisomy 21 is cost effective and results in a higher overall detection rate for trisomy 21.